Genetic polydactyly / arhinencephaly mouse (Pdn / Pdn) is a homologue of Greig cephalopolysyndactyly syndrome.

多指小鼠纯合子(PDN/PDN)表现为轴前多指和鼻头畸形，其致病基因被认为是染色体13A2-3上的Gli3。Greig头多指并指综合征(GCPS)具有特殊的面部特征，包括宽大的鼻根和远指，以及足部和手部的多指和并指。其致病基因为染色体7p13上的GLI3。从Gli3和Gli3基因的高度同源性、表型的相似性和染色体的同源性来看，pDn/pDn被认为是人…的小鼠同源物，其发育机制可以推测为gcp的发育机制。本研究对pDn/pdn小鼠的发育机制进行了研究，特别是在嗅神经、嗅球形成和三叉神经方面。1)用DiI法研究了嗅神经纤维投射到妊娠第12天的端脑的情况正常小鼠胚胎在妊娠第13天，端脑前部突起形成嗅球原基。而在PDN/PDN小鼠胚胎发育的各个阶段，嗅神经纤维均未附着并侵入端脑。由此推测，嗅球突起不是由于嗅神经纤维不附着在端脑引起的。2)嗅神经纤维不侵犯中枢神经系统，嗅神经纤维在前脑或大脑半球下的脑膜下形成缠绕的团块。在电子显微镜下，PDN/PDN新生儿筛板上的嗅神经缠结处未见突触。3)PDN/PDN未形成嗅球和副嗅球。但在PDN/PDN中，用抗OCAM(嗅细胞黏附分子)抗体进行免疫组织化学染色，可检测到构成嗅球的原始二尖瓣/簇状细胞。这意味着，端脑前部注定要分化为无嗅神经支配的二尖瓣/簇状细胞。然后，嗅神经纤维的神经支配导致嗅球从端脑突起，直至妊娠第12天。因此，有人认为形成嗅球的机制有两个步骤。4)PDN/PDN在出生后不久死亡，没有吮吸母亲的乳汁。据认为，新生的老鼠会用胡须或嗅觉来搜索它们母亲的乳头。胡须由三叉神经支配。用抗神经丝抗体进行免疫组织化学染色，观察了PDN/PDN小鼠胚胎的三叉神经纤维。PDN/PDN的三叉神经节、三叉神经纤维束的突起及其胡须毛囊的神经支配正常。PDN/PDN存在上述嗅觉系统的异常，因此，PDN/PDN的哺乳功能障碍被认为是由嗅觉系统功能障碍引起的。较少

The homozygote of Polydactyly mouse (Pdn/Pdn) shows preaxial polydactyly and arhinecephaly, and its responsible gene has been considered to be Gli3 on chromosome 13A2-3. Greig cephalopolysyndactyly syndrome (GCPS) shows peculiar facial feature including broad nasal root and telecanthus, and polydactyly arid syndactyly both In the foot and hand. Its responsible gene is GLI3 on chromosome 7p13. From the high homology between Gli3 and GLI3 genes, the similarity of phenotypes, and synteny of their chromosomes, Pdn/Pdn was considered to be a mouse homologue of human GCPS.It was thought that developmental mechanisms in Pdn/Pdn mouse can be extrapolated to the developmental mechanism of GCPS.In this study, developmental mechanisms of Pdn/Pdn mouse was investigated especially in the olfactory nerve, olfactory bulb formation and trigeminal nerve.1) Olfactory nerve fiber projection were investigated by DiI.The olfactory nerve fibers attached and invaded into the telencephalon on day 12 of gestat … More ion, and anterior part of telencephalon protruded to form the olfactory bulb primodium on day 13 of gestation in the normal mouse embryos. While, the olfactory nerve fibers did not attach and invade the telencephalon during any developmental stages in Pdn/Pdn mouse embryos. From thIs phenomenon, it was suggested that the protrusion of the olfactory bulb was not induced by the non-attachment of the olfactory nerve fibers to the telencephalon.2) Olfactory nerve fibers did not invade the central nervous systems, and olfactory nerve fibers formed a tangled mass under the forebrain or cerebral hemisphere in the meninges in Pdn/Pdn embryos. In the electron microscopic observations, there were no synaps in the tangle of the olfactory nerve on the cribriform plate in Pdn/Pdn newborns.3) Olfactory bulb and accessory olfactory bulb were not formed in Pdn/Pdn. But, primordial mitral/tufted cells which construct the olafactory bulb were detected by the immunohistochemical staining using anti-OCAM (olfactory cell adhesion molecule) antibody in Pdn/Pdn. That means, anterior part of telencephalon has a destine to differentiate to be the mitral/tufted cells without olfactory nerve innervation. Then, protrusion of the olfactory bulb from the telencephalon is induced by the innervation of the olfactory nerve fibers till day 12 of gestation. Thus, it was suggested that the mechanisms to form the olfactory bulb have 2 steps.4) Pdn/Pdn die soon after birth without sucking their mother's milk. it was considered that mouse newborns search their mother's nipples using either their whisker or olfaction. Whisker is innervated by the trigeminal nerve. Trigeminal nerve fibers in Pdn/Pdn mouse embryos were investigated by the immunohistochemical staining using anti-neurofilament antibody. Trigeminal ganglion, outgrowth of trigeminla nerve fiber bundles, and its innervation of the whisker follicles were normal in Pdn/Pdn. Pdn/Pdn has abnormalities in the olfactory system as mentioned above, so suckling dysfuction in Pdn/Pdn was considered to be caused by the dysfunction of the olfactory system. Less